Diisopropylethylamine → HCID 10887168, compound

HRID 2104329Notes

Reaction equation

HRID 2104329 reaction equation
Cl.[CH3:2]N(C)CCCN=C=NCC.[C:13]([O:17][C:18]([NH:20][C:21]([CH3:29])([CH3:28])[CH2:22]/[CH:23]=[CH:24]/[C:25]([OH:27])=O)=[O:19])([CH3:16])([CH3:15])[CH3:14].ON1C2N=CC=CC=2N=N1.[CH2:40]([C@@H:47]([N:60]([CH3:77])[C:61](=[O:76])[C@H:62]([NH:74][CH3:75])[CH2:63][C:64]1[CH:73]=[CH:72][C:71]2[C:66](=[CH:67][CH:68]=[CH:69][CH:70]=2)[CH:65]=1)[C:48]([N:50]1[CH2:55][CH2:54][CH2:53][C@@H:52]([CH2:56][N:57]([CH3:59])[CH3:58])[CH2:51]1)=[O:49])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C(N(C(C)C)C(C)C)C>ClCCl.CN(C)C=O.C(OCC)(=O)C>[C:13]([O:17][C:18](=[O:19])[NH:20][C:21]1([CH2:22]/[CH:23]=[CH:24]/[C:25](=[O:27])[N:74]([C@@H:62]([C:61](=[O:76])[N:60]([C@H:47]([CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:48]([N:50]2[CH2:55][CH2:54][CH2:53][C@@H:52]([CH2:56][N:57]([CH3:58])[CH3:59])[CH2:51]2)=[O:49])[CH3:77])[CH2:63][C:64]2[CH:73]=[CH:72][C:71]3[C:66](=[CH:67][CH:68]=[CH:69][CH:70]=3)[CH:65]=2)[CH3:75])[CH2:29][CH2:2][CH2:28]1)([CH3:14])([CH3:15])[CH3:16]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acidHCID 11113984HCID 11113984, compound

Product 1

HCID 10887168HCID 10887168, compoundYield 94.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (85 mg, 0.44 mmol) was added to a solution of (2E)-5-(tert-butoxycarbonylamino)-5-methylhex-2-enoic acid (113 mg, 0.44 mmol) and 1-hydroxy-7-azabenzotriazole (60 mg, 0.44 mmol) in dichloromethane (5 ml) and N,N-dimethylformamide (5 ml). The reaction mixture was stirred for 20 mm at 0° C. A solution of (2R)—N-[(1R)-1-benzyl-2-((3S)-3-((dimethylamino)methyl)piperidin-1-yl)-2-oxoethyl]-N-methyl-2-(methylamino)-3-(2-naphthyl)propionamide (228 mg, 0.44 mmol) in dichloromethane (10 ml) and ethyldiisopropylamine (0.07 ml, 0.44 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (70 ml) and washed with a saturated aqueous solution of sodium hydrogen carbonate (70 ml). The aqueous phase was extracted with ethyl acetate (3×50 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (40 g), using dichlormethane/methanol/25% aqueous ammonia (100:10:1) as eluent, to give 314 mg of (1-{(2E)-3-[N-((1R)-1-{N-[(1R)-1-benzyl-2-((3S)-3-((dimethylamino)methyl)piperidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylcarbamoyl]allyl}cyclobutyl)-carbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with a saturated aqueous solution of sodium hydrogen carbonate (70 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×50 ml)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. customThe solvent was removed in vacuo
  7. customThe crude product was purified by flash chromatography on silica (40 g)

Sources & evidence

ORD record
ord-176f736670f34c1f856e34bfa3629d44
Source dataset
uspto-grants-2009_08
Patent number
US07576062B2

Reaction notes

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